Affymetrix GeneChip microarray technology is constantly evolving with regard to the development of new arrays, expression and genotyping assays, and improved instrumentation. The increase in the size and variety of arrays coupled with their exponentially increasing use has greatly exacerbated the need for more advanced and more highly automated instrumentation. Automated methods for microarray analysis are less labor-intensive, less costly on a per sample basis, more reproducible, and are much easier to standardize across different laboratories. The Keck GeneChip facility is very heavily used to analyze gene expression and to genotype DNA. Since its founding in 2003, the GeneChip facility has analyzed >4,000 samples from >115 investigators at Yale and at 22 other institutions. The demand for services has increased by >50% in each of the last three years. Additionally, the Keck GeneChip Resource is part of the newly funded Yale Microarray Center for Research on the Nervous System. As one of four laboratories responsible for providing microarray technologies to 10,000 neuroscientists from 15 institutes in the NIH Neuroscience Blueprint, this recent award will very substantially increase the demand for Keck GeneChip services and will ensure that the requested instrumentation is used to its full capacity. In this regard, the requested GeneChip Automation Platform and MegAllele System would allow the Keck Lab to meet the anticipated increase in demand for existing services, to bring custom genotyping within reach of its users, and also would improve the reliability of the resulting data by reducing operator-to-operator variability. Funding this application would enable the GeneChip Resource to bring state-of-the-art microarray technologies to bear on several important diseases including epilepsy, psychiatric disorders, autism, cardiovascular disorders, and cancer. The strengths of this proposal include a very diverse and productive investigator user base; the experience of the PI in overseeing the Keck Affymetrix Lab and its associated Yale/NIH Microarray Center; the experience of Co-PI, K. Williams, in overseeing numerous large, multi-investigator NIH contracts and Centers; the biotechnological, statistical and database expertise of the PI and other key personnel; and the extensive infrastructure and complementary support from the Keck Lab and its associated NIH-funded Centers (e.g., the Yale/NIDA Neuroproteomics Center and the new Center for High Performance Computation in Biomedicine). If given the opportunity, the PI and key personnel will do absolutely everything in their power to ensure that the requested instrumentation has a very positive and long-lasting impact on biomedical research that will extend well beyond Yale. [unreadable] [unreadable] [unreadable]